tbuckley/cabot-search huggingface dataset:
Uncovering the Potential of CD40 Agonism to Enhance Immune Checkpoint Blockade
Authors: Richard C. Wu, Jason J. Luke
Journal: Clinical Cancer Research (2023)

Summary In this CCR Translations, we discuss the therapeutic potential of CD40 agonism, which stimulates antigen-presenting cells (APC) to activate effector T and NK cells. CD40 agonism may lead to development of an interferon-activated, T cell–inflamed tumor microenvironment and has the potential to facilitate long-term response with immune checkpoint blockade. See related article by Weiss et al., p. 74
Wnt/β-catenin and NFκB signaling synergize to trigger growth factor-free regeneration of adult primary human hepatocytes
Authors: Nuria Oliva-Vilarnau, Christian M. Beusch, Pierre Sabatier, Eirini Sakaraki, Amelie Tjaden, Lukas Graetz, Florian A. Büttner, Debra Dorotea, My Nguyen, Filip Bergqvist, Yvonne Sundström, Susanne Müller, Roman A. Zubarev, Gunnar Schulte, Claudia Tredup, Roberto Gramignoli, Uwe J.F. Tietge, Volker M. Lauschke
Journal: Hepatology (2023)

Background and Aims: The liver has a remarkable capacity to regenerate, which is sustained by the ability of hepatocytes to act as facultative stem cells that, while normally quiescent, re-enter the cell cycle after injury. Growth factor signaling is indispensable in rodents, whereas Wnt/β-catenin is not required for effective tissue repair. However, the molecular networks that control human liver regeneration remain unclear. Methods: Organotypic 3D spheroid cultures of primary human or murine hepatocytes were used to identify the signaling network underlying cell cycle re-entry. Furthermore, we performed chemogenomic screening of a library enriched for epigenetic regulators and modulators of immune function to determine the importance of epigenomic control for human hepatocyte regeneration. Results: Our results showed that, unlike in rodents, activation of Wnt/β-catenin signaling is the major mitogenic cue for adult primary human hepatocytes. Furthermore, we identified TGFβ inhibition and inflammatory signaling through NF-κB as essential steps for the quiescent-to-regenerative switch that allows Wnt/β-catenin-induced proliferation of human cells. In contrast, growth factors, but not Wnt/β-catenin signaling, triggered hyperplasia in murine hepatocytes. High-throughput screening in a human model confirmed the relevance of NFκB and revealed the critical roles of polycomb repressive complex 2, as well as of the bromodomain families I, II, and IV. Conclusions: This study revealed a network of NFκB, TGFβ, and Wnt/β-catenin that controls human hepatocyte regeneration in the absence of exogenous growth factors, identified novel regulators of hepatocyte proliferation, and highlighted the potential of organotypic culture systems for chemogenomic interrogation of complex physiological processes.
Progressive Cranial Neuropathy
Authors: David S. Buchberger, Samantha K. Cook, Shlomo A. Koyfman
Journal: JAMA Neurology (2023)

A 68-year-old man had right facial weakness with a droop, slurred speech, and eyelid ptosis that progressed over 5 years from right temple numbness and did not respond to gabapentin or steroids. What is your diagnosis?
FLight Biofabrication Supports Maturation of Articular Cartilage with Anisotropic Properties
Authors: Anna Puiggalí‐Jou, Riccardo Rizzo, Angela Bonato, Philipp Fisch, Simone Ponta, Daniel M. Weber, Marcy Zenobi‐Wong
Journal: Advanced Healthcare Materials (2023)

Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation. The arrangement of the extracellular matrix (ECM) plays a fundamental role in determining the mechanical and biological functions of the tissue. In this study, it is shown that a novel light-based approach, Filamented Light (FLight) biofabrication, can be used to generate highly porous, 3D cell-instructive anisotropic constructs that lead to directional collagen deposition. Using a photoclick-based photoresin optimized for cartilage tissue engineering, a significantly improved maturation of the cartilaginous tissues with zonal architecture and remarkable native-like mechanical properties is demonstrated.
Stronger Together: Cancer Clones Cooperate to Alleviate Growth Barriers in Critical Cancer Progression Transitions
Authors: Zachary T. Compton, Diego Mallo, Carlo C. Maley
Journal: Cancer Research (2023)

Abstract Hershey and colleagues recently showed how clones in a triple-negative breast cancer cell line cooperate for their mutual fitness benefit. In this system, clones exchange soluble metabolites to increase their in vitro growth rate at low population densities, therefore mitigating the documented growth barrier that reduces individual fitness in small tumor cell populations (Allee effect). Such cooperation could aid important transitions in cancer progression in which cancer cell populations are small, like invasion or metastasis. Using orthotopic transplantation, the authors demonstrate that this cooperation is functional in one such transition in vivo, increasing the metastatic load and number of metastases, which are usually polyclonal. Together, these findings highlight the need to consider ecologic interactions to properly understand tumor growth dynamics, and how they complement the standing evolutionary model of cancer progression in our quest to understand and treat cancer.
A Curious Case of Intermittent Negative Deflections Preceding the QRS Complexes
Authors: János Tomcsányi, Kristóf Tomcsányi, Béla Bózsik
Journal: JAMA Internal Medicine (2023)

This case report describes a patient in their 60s who developed apparent abnormal Q waves and severe hypomagnesemia while receiving chemotherapy for metastatic rectal carcinoma.
Errors in Text, Table, and Figure
Journal: JAMA Pediatrics (2023)

Letter titled "Trends in Obesity Prevalence Among Children and Adolescents Aged 2 to 19 Years in the US From 2011 to 2020," 1 published online first on July 25, 2022, and in the October 2022 issue of JAMA Pediatrics, there was an error in the analyses of the mobile examination clinic (MEC) weights.During the final analysis, the weights were removed so as to include race and ethnicity as a covariate.Per the National Health and Nutrition Examination Survey, inclusion of the MEC weights is necessary to make the prevalence data nationally representative.To address this error, calculations were performed again to include MEC weights through all stages of the analyses.As a result, the updated analyses resulted in corrections to many of the prevalence rates reported in the text, Table , andFigure.In addition, the trends for increased obesity in adolescents aged 12 to 19 years, non-Hispanic White children and adolescents, and girls changed from significant to not significant.A Letter of Explanation 2 has been published that explains the errors.This article was corrected online.
Strength Training Is Associated With Less Knee Osteoarthritis: Data From the Osteoarthritis Initiative
Authors: Grace H. Lo, Michael J. Richard, Timothy E. McAlindon, Andrea M. Kriska, Lori Lyn Price, Bonny Rockette‐Wagner, Charles B. Eaton, Marc C. Hochberg, C. Kent Kwoh, Michael C. Nevitt, Jeffrey B. Driban
Journal: Arthritis & Rheumatology (2023)

We aimed to evaluate the relationship of a history of strength training with symptomatic and structural outcomes of knee osteoarthritis (OA). This study was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), a multicenter prospective longitudinal observational study. Data were collected at four OAI clinical sites: Memorial Hospital of Rhode Island, the Ohio State University, the University of Pittsburgh, and the University of Maryland/Johns Hopkins. The study included 2,607 participants with complete data on strength training, knee pain, and radiographic evidence of knee OA (male, 44.2%; mean ± SD age 64.3 ± 9.0 years; mean ± SD body mass index 28.5 ± 4.9 kg/m2 ). We used a self-administered questionnaire at the 96-month OAI visit to evaluate the exposure of strength training participation during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and ≥50 years old). The outcomes (dependent variables) were radiographic OA (ROA), symptomatic radiographic OA (SOA), and frequent knee pain. The fully adjusted odds ratios (95% confidence interval) for frequent knee pain, ROA, and SOA among those who participated in strength training any time in their lives were 0.82 (0.68-0.97), 0.83 (0.70-0.99), and 0.77 (0.63-0.94), respectively. Findings were similar when looking at the specific age ranges. Strength training is beneficial for future knee health, counteracting long-held assumptions that strength training has adverse effects.
Multitarget Stool RNA Test for Colorectal Cancer Screening
Authors: Erica K. Barnell, Elizabeth M. Wurtzler, Julie La Rocca, Thomas Fitzgerald, Jessica Petrone, Yansheng Hao, Yiming Kang, Faith L. Holmes, David A. Lieberman
Journal: JAMA (2023)

Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk individuals 45 years or older.
Supramolecular nanofiber of indomethacin derivative confers highly cyclooxygenase-2 (COX-2) selectivity and boosts anti-inflammatory efficacy
Authors: Deqing Lin, Xiaoning Xu, Lin Chen, Lei Chen, Mengyun Deng, Jinrun Chen, Zhibin Ren, Lei Lei, Jiaqing Wang, Jie Deng, Xingyi Li
Journal: Journal of Controlled Release (2023)
Development of Fibro-PeN, a clinical prediction model for moderate-to-severe fibrosis in children with nonalcoholic fatty liver disease
Authors: Andrew Wang, Amanda L. Blackford, Cynthia Behling, Laura A. Wilson, Kimberly P. Newton, Stavra A. Xanthakos, Mark H. Fishbein, Miriam B. Vos, Marialena Mouzaki, Jean P. Molleston, Ajay K. Jain, Paula Hertel, Kathryn Harlow Adams, Jeffrey B. Schwimmer
Journal: Hepatology (2023)

Background and Aims: Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD. Approach and Results: We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77–0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis. Conclusion: Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.
Hospital Admissions for Abusive Head Trauma Before and During the COVID-19 Pandemic
Authors: Nathan L. Maassel, Elena Graetz, Eric B. Schneider, Andrea G. Asnes, Daniel G. Solomon, John M. Leventhal
Journal: JAMA Pediatrics (2023)

Importance Several studies have demonstrated a decrease in the occurrence of child abuse in the US since the start of the COVID-19 pandemic. This finding has generated concern for missed cases due to the initial lockdowns and lack of childcare resources. Determining the association of the pandemic on hospitalizations for severe forms of abuse is essential to focus preventive efforts. Objective To examine trends in abusive head trauma (AHT) before and during the COVID-19 pandemic. Design, Setting, and Participants Retrospective, multicenter, repeated cross-sectional study, conducted January 1, 2016, through April 30, 2022, with data from tertiary care children’s hospitals and contributors to the Pediatric Health Information System. Data were obtained for 2380 hospitalizations of children younger than 5 years with International Classification of Diseases, Tenth Revision, Clinical Modification codes for both abuse and head trauma. Main Outcomes and Measures Monthly hospitalizations were analyzed using interrupted time-series analysis. Hospitalization severity (eg, intensive care unit stay) and clinical characteristics (subdural hemorrhages and retinal hemorrhages) were compared before and after the start of the pandemic. Results We identified 2380 hospitalizations due to AHT (median age, 140 [IQR, 75.0-325.5] days) from 45 hospitals. The mean (SD) monthly incidence of AHT was 34.3 (5.8) before the COVID-19 pandemic compared with 25.6 (4.2) during COVID-19 (a 25.4% decrease). When the pre–COVID-19 and during COVID-19 periods were compared, there were no significant differences in severity or clinical characteristics. On interrupted time-series analysis, there was a significant decrease in the number of monthly hospitalizations (−8.1; 95% CI, −12.41 to −3.72; P &amp;amp;lt; .001) in the first month of the pandemic. In the subgroup of children younger than 1 year, there was a significant decrease in monthly hospitalizations at the onset of the pandemic (−8.2; 95% CI, −12.02 to −4.43; P &amp;amp;lt; .001) followed by a significant temporal increase across the COVID-19 period ( P = .01). Conclusions and Relevance The findings of this cross-sectional study suggest there was a significant decrease in monthly hospitalizations for AHT following the start of the pandemic in March 2020. Although there was no corresponding increase in hospitalization severity, the decrease during the pandemic may have been transient, as monthly hospitalizations for children younger than 1 year increased significantly over time during COVID-19, after the initial decrease.
Comprehensive vasodilatation in women with acute heart failure: Novel insights from the <scp>GALACTIC</scp> randomized controlled trial
Authors: Desiree Wussler, Maria Belkin, Micha T. Maeder, Joan Walter, Samyut Shrestha, Karolina Kupska, Michelle Stierli, Dayana Flores, Nikola Kozhuharov, Danielle Menosi Gualandro, Mucio Tavares de Oliveira Junior, Zaid Sabti, Markus Noveanu, Thenral Socrates, Antoni Bayés‐Genis, Alessandro Sionis, Patrick Simon, Eleni Michou, Samuel Gujer, Tommaso Gori, Philip Wenzel, Otmar Pfister, Nisha Arenja, Richard Kobza, Hans Rickli, Tobias Breidthardt, Thomas Münzel, Christian Mueller
Journal: European Journal of Heart Failure (2023)
Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study
Authors: Andrew D. Leavitt, Barbara A. Konkle, Kimo C. Stine, Nathan Visweshwar, Thomas J. Harrington, Adam Giermasz, Steven Arkin, Annie Fang, Frank Plonski, Anne Yver, Florence Ganne, Delphine Agathon, Maria de los Angeles Resa, Li-Jung Tseng, Gregory Di Russo, Bettina M. Cockroft, Liching Cao, Jeremy Rupon
Journal: Blood (2023)

Abstract Patients with hemophilia A require exogenous factor VIII (FVIII) or nonfactor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector–based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain–deleted human F8 gene. In the ongoing phase 1/2, dose-ranging Alta study, 4 sequential cohorts of male participants with severe hemophilia A received a single IV dose of giroctocogene fitelparvovec. The primary end points are safety and changes in circulating FVIII activity. Interim results up to 214 weeks after treatment for all participants are presented. Eleven participants were dosed. Increases in alanine and aspartate aminotransferases were the most common treatment-related adverse events (AEs), which resolved with corticosteroid administration. Two treatment-related serious AEs (hypotension and pyrexia) were reported in 1 participant within 6 hours of infusion and resolved within 24 hours after infusion. At the highest dose level (3 × 1013 vg/kg; n = 5), the mean circulating FVIII activity level at week 52 was 42.6% (range, 7.8%-122.3%), and at week 104 it was 25.4% (range, 0.9%-71.6%) based on a chromogenic assay. No liver masses, thrombotic events, or confirmed inhibitors were detected in any participant. These interim 104-week data suggest that giroctocogene fitelparvovec is generally well tolerated with appropriate clinical management and has the potential to provide clinically meaningful FVIII activity levels, as indicated by the low rate of bleeding events in the highest dose cohort. This trial was registered at www.clinicaltrials.gov as #NCT03061201.
Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France
Authors: Francesco Peyronel, Julien Haroche, Corrado Campochiaro, Francesco Pegoraro, Zahir Amoura, Alessandro Tomelleri, Martina Mazzariol, Matthias Papo, Giulio Cavalli, Giuseppe D. Benigno, Paride Fenaroli, Chrysanthos Grigoratos, Maria C. Mengoli, Arturo Bonometti, Emilio Berti, Gustavo Savino, Mauro Cives, Iria Neri, Gaetano Pacinella, Antonino Tuttolomondo, Massimo Marano, Francesco Muratore, Andreina Manfredi, Alessandro Broccoli, Pier L. Zinzani, Biagio Didona, Chiara Massaccesi, Andrea Buono, Enrico Ammirati, Vito Di Lernia, Lorenzo Dagna, Augusto Vaglio, Fleur Cohen-Aubart
Journal: Blood (2023)
Tissue-infiltrating alloreactive T cells require Id3 to deflect PD-1–mediated immune suppression during GVHD
Authors: Ying Wang, Shan He, Gennaro Calendo, Tien Bui, Yuanyuan Tian, Che Young Lee, Yan Zhou, Xin Zhao, Ciril Abraham, Wenbin Mo, Mimi Chen, Ruqayyah Sanders-Braggs, Jozef Madzo, Jean-Pierre Issa, Elizabeth O. Hexner, David L. Wiest, Ran Reshef, Hai-Hui Xue, Yi Zhang
Journal: Blood (2023)
Annals Graphic Medicine - Dr. Mom: ICD-10 Codes for Parents
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2023)

Web Exclusives24 October 2023Annals Graphic Medicine - Dr. Mom: ICD-10 Codes for ParentsFREEGrace E. Farris, MDGrace E. Farris, MDUniversity of Texas, Austin, Texas (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G23-0046 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Grace E. Farris, MDAffiliations: University of Texas, Austin, Texas (G.E.F.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0020.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears quarterly in Annals Graphic Medicine at Annals.org.This article was published at Annals.org on 24 October 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current Issue November 2023Volume 176, Issue 11 ePublished: 24 October 2023 Issue Published: November 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Let’s Talk About Respiratory Swings!
Authors: Horst Olschewski, Katarina Zeder, Philipp Douschan, Teresa Sassmann, Vasile Foris, Andrea Olschewski, Gabor Kovacs
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Let’s Talk About Respiratory Swings!." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Inappropriate Prescribing to Older Patients by Nurse Practitioners and Primary Care Physicians
Authors: Johnny Huynh, Sahil A. Alim, David C. Chan, David M. Studdert
Journal: Annals of Internal Medicine (2023)

Many U.S. states have legislated to allow nurse practitioners (NPs) to independently prescribe drugs. Critics contend that these moves will adversely affect quality of care.To compare rates of inappropriate prescribing among NPs and primary care physicians.Rates of inappropriate prescribing were calculated and compared for 23 669 NPs and 50 060 primary care physicians who wrote prescriptions for 100 or more patients per year, with adjustment for practice experience, patient volume and risk, clinical setting, year, and state.29 states that had granted NPs prescriptive authority by 2019.Medicare Part D beneficiaries aged 65 years or older in 2013 to 2019.Inappropriate prescriptions, defined as drugs that typically should not be prescribed for adults aged 65 years or older, according to the American Geriatrics Society's Beers Criteria.Mean rates of inappropriate prescribing by NPs and primary care physicians were virtually identical (adjusted odds ratio, 0.99 [95% CI, 0.97 to 1.01]; crude rates, 1.63 vs. 1.69 per 100 prescriptions; adjusted rates, 1.66 vs. 1.68). However, NPs were overrepresented among clinicians with the highest and lowest rates of inappropriate prescribing. For both types of practitioners, discrepancies in inappropriate prescribing rates across states tended to be larger than discrepancies between these practitioners within states.The Beers Criteria addresses the appropriateness of a selected subset of drugs and may not be valid in some clinical settings.Nurse practitioners were no more likely than physicians to prescribe inappropriately to older patients. Broad efforts to improve the performance of all clinicians who prescribe may be more effective than limiting independent prescriptive authority to physicians.The Robert Wood Johnson Foundation and National Science Foundation.